Abstract 3303: High homogeneity of mesothelin expressionin primary and metastatic ovarian cancer
Authors: Sören Weidemann, Natalia Gorbokon, Maximilian Lennartz, Claudia Hube-Magg, Christoph Fraune, Christian Bernreuther, Till Clauditz, Frank Jacobsen, Kristina Jansen, Barbara Schmalfeldt, Linn Wölber, Peter Paluchowski, Enikö Berkes, Uwe Heilenkötter, Guido Sauter, Ria Uhlig, Waldemar Wilczak, Stefan Steurer, Ronald Simon, Till Krech, Andreas Marx, Eike Burandt
Journal: Cancer Research (2023)

Abstract Background: Mesothelin is a glycosylphosphatidylinositol-anchored cell surface protein of widely unknown function that may play a role in tumor growth control. Because mesothelin is overexpressed in a variety of human cancer types including ovarian cancers, it represents an attractive target for novel therapies employing adaptive T-cell transfer in these tumors. However, tumor heterogeneity is a challenge for targeted therapies. Methods: To study the extent of heterogeneity of mesothelin overexpression in primary ovarian cancers and their peritoneal and lymph node metastases, a tissue microarray (TMA) was constructed from multiple sites of 220 ovarian cancers and analyzed by immunohistochemistry. One tissue core each was taken from up to 18 different tumor blocks per cancer, resulting in a total of 2,460 tissue spots from 423 tumor sites (188 primary cancers, 162 peritoneal carcinosis and 73 lymph node metastases). Results: Positive mesothelin expression was found in 2,041 of the 2,342 (87%) arrayed tissue spots and in 372 of the 392 (95%) tumor sites that were interpretable for mesothelin immunohistochemistry. Intratumoral heterogeneity was found in 23% of 168 primary cancer sites interpretable for mesothelin and decreased to 12% in 154 peritoneal carcinosis and to 6% in 71 lymph node metastases (p&amp;lt;0.0001). Heterogeneity between the primary tumor and matched peritoneal carcinosis was found in 16% of 102 cancers with interpretable mesothelin results. In these cancers, the mesothelin status switched from positive in the primary tumor to negative in the peritoneal carcinosis (3 cancers) in or vice versa (2 cancers), or a mixture of positive and negative peritoneal carcinoses was found (11 cancers). No such switch was seen between the mesothelin-interpretable primary tumors and their nodal metastases of 59 cancers, and only one mesothelin-positive tumor had a mixture of positive and negative lymph node metastases. Conclusions: Our data demonstrate that mesothelin expression is frequent and highly homogeneous in ovarian cancer and prompt for future anti-mesothelin therapy studies in this tumor type. Citation Format: Sören Weidemann, Natalia Gorbokon, Maximilian Lennartz, Claudia Hube-Magg, Christoph Fraune, Christian Bernreuther, Till Clauditz, Frank Jacobsen, Kristina Jansen, Barbara Schmalfeldt, Linn Wölber, Peter Paluchowski, Enikö Berkes, Uwe Heilenkötter, Guido Sauter, Ria Uhlig, Waldemar Wilczak, Stefan Steurer, Ronald Simon, Till Krech, Andreas Marx, Eike Burandt. High homogeneity of mesothelin expressionin primary and metastatic ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3303.